Recent breakthroughs in innovative elements, multidimensional enhancements, derived technologies, and novel applications of PROTACs

Autor: Si-Han Zhang, Na Zeng, Jin-Zhou Xu, Chen-Qian Liu, Meng-Yao Xu, Jian-Xuan Sun, Ye An, Xing-Yu Zhong, Lin-Tao Miao, Shao-Gang Wang, Qi-Dong Xia
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Biomedicine & Pharmacotherapy, Vol 180, Iss , Pp 117584- (2024)
Druh dokumentu: article
ISSN: 0753-3322
DOI: 10.1016/j.biopha.2024.117584
Popis: Proteolysis Targeting Chimera (PROTAC) is an emerging and evolving technology based on targeted protein degradation (TPD). Small molecule PROTACs have shown great efficacy in degrading disease-specific proteins in preclinical and clinical studies, but also showed various limitations. In recent years, new technologies and advances in TPD have provided additional optimized strategies based on conventional PROTACs that can overcome the shortcomings of conventional PROTACs in terms of undruggable targets, bioavailability, tissue-specificity, spatiotemporal control, and degradation scope. In addition, some designs of special targeting chimeras and applications based on multidisciplinary science have shed light on novel therapeutic modalities and drug design. However, each improvement has its own advantages, disadvantages and application conditions. In this review, we summarize the exploration of PROTAC elements, depict a landscape of improvements and derived concepts of PROTACs, and expect to provide perspectives for technological innovations, combinations and applications in future targeting chimera design.
Databáze: Directory of Open Access Journals